The integrin family of cell adhesion receptors regulates a diverse array of cellular functions crucial to the initiation, progression and metastasis of solid tumours. The importance of integrins in several cell types that affect tumour progression has made them an appealing target for cancer therapy. Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. These exciting clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.

/pdf/integrins-in-cancer-biological-implications-and-therapeutic-2ejzg8fop4.pdf

Integrins in cancer: biological implications and therapeutic opportunities

On death and dying

http://tissueeng.net/lab/papers/GelMA.pdf

Cell-laden microengineered gelatin methacrylate hydrogels.

Econometric policy evaluation: A critique

Analysis of cellular mechanotransduction, the mechanism by which cells convert mechanical signals into biochemical responses, has focused on identification of critical mechanosensitive molecules and cellular components. Stretch-activated ion channels, caveolae, integrins, cadherins, growth factor receptors, myosin motors, cytoskeletal filaments, nuclei, extracellular matrix, and numerous other structures and signaling molecules have all been shown to contribute to the mechanotransduction response. However, little is known about how these different molecules function within the structural context of living cells, tissues, and organs to produce the orchestrated cellular behaviors required for mechanosensation, embryogenesis, and physiological control. Recent work from a wide range of fields reveals that organ, tissue, and cell anatomy are as important for mechanotransduction as individual mechanosensitive proteins and that our bodies use structural hierarchies (systems within systems) composed of interconnected networks that span from the macroscale to the nanoscale in order to focus stresses on specific mechanotransducer molecules. The presence of isometric tension (prestress) at all levels of these multiscale networks ensures that various molecular scale mechanochemical transduction mechanisms proceed simultaneously and produce a concerted response. Future research in this area will therefore require analysis, understanding, and modeling of tensionally integrated (tensegrity) systems of mechanochemical control.

/pdf/cellular-mechanotransduction-putting-all-the-pieces-together-46w4qt2qc2.pdf

Cellular mechanotransduction: putting all the pieces together again.

Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Although much is known about how soluble factors influence macrophage polarization, relatively little is known about how physical cues present in the extracellular environment might modulate proinflammatory (M1) vs. prohealing (M2) activation. Specifically, the role of cell shape has not been explored, even though it has been observed that macrophages adopt different geometries in vivo. We and others observed that macrophages polarized toward different phenotypes in vitro exhibit dramatic changes in cell shape: M2 cells exhibit an elongated shape compared with M1 cells. Using a micropatterning approach to control macrophage cell shape directly, we demonstrate here that elongation itself, without exogenous cytokines, leads to the expression of M2 phenotype markers and reduces the secretion of inflammatory cytokines. Moreover, elongation enhances the effects of M2-inducing cytokines IL-4 and IL-13 and protects cells from M1-inducing stimuli LPS and IFN-γ. In addition shape- but not cytokine-induced polarization is abrogated when actin and actin/myosin contractility are inhibited by pharmacological agents, suggesting a role for the cytoskeleton in the control of macrophage polarization by cell geometry. Our studies demonstrate that alterations in cell shape associated with changes in ECM architecture may provide integral cues to modulate macrophage phenotype polarization.

/pdf/modulation-of-macrophage-phenotype-by-cell-shape-1f7qrtfnnt.pdf

Modulation of macrophage phenotype by cell shape

Spatial patterns of cellular growth generate mechanical stresses that help to push, fold, expand, and deform tissues into their specific forms. Genetic factors are thought to specify patterns of growth and other behaviors to drive morphogenesis. Here, we show that tissue form itself can feed back to regulate patterns of proliferation. Using microfabrication to control the organization of sheets of cells, we demonstrated the emergence of stable patterns of proliferative foci. Regions of concentrated growth corresponded to regions of high tractional stress generated within the sheet, as predicted by a finite-element model of multicellular mechanics and measured directly by using a micromechanical force sensor array. Inhibiting actomyosin-based tension or cadherin-mediated connections between cells disrupted the spatial pattern of proliferation. These findings demonstrate the existence of patterns of mechanical forces that originate from the contraction of cells, emerge from their multicellular organization, and result in patterns of growth. Thus, tissue form is not only a consequence but also an active regulator of tissue growth.

/pdf/emergent-patterns-of-growth-controlled-by-multicellular-form-1b3qnai9aw.pdf

Emergent patterns of growth controlled by multicellular form and mechanics.

In this paper, we extend existing work on latent attribute inference by leveraging the principle of homophily: we evaluate the inference accuracy gained by augmenting the user features with features derived from the Twitter profiles and postings of her friends. We consider three attributes which have varying degrees of assortativity: gender, age, and political affiliation. Our approach yields a significant and robust increase in accuracy for both age and political affiliation, indicating that our approach boosts performance for attributes with moderate to high assortativity. Furthermore, different neighborhood subsets yielded optimal performance for different attributes, suggesting that different subsamples of the user's neighborhood characterize different aspects of the user herself. Finally, inferences using only the features of a user's neighbors outperformed those based on the user's features alone. This suggests that the neighborhood context alone carries substantial information about the user.

https://www.aaai.org/ocs/index.php/ICWSM/ICWSM12/paper/download/4713/5013

Homophily and Latent Attribute Inference: Inferring Latent Attributes of Twitter Users from Neighbors

Macrophages are tissue-resident immune cells that play a critical role in maintaining homeostasis and fighting infection. In addition, these cells are involved in the progression of many pathologies including cancer and atherosclerosis. In response to a variety of microenvironmental stimuli, macrophages can be polarized to achieve a spectrum of functional phenotypes. This review will discuss some emerging evidence in support of macrophage phenotypic regulation by physical and mechanical cues. As alterations in the physical microenvironment often underlie pathophysiological states, an understanding of their effects on macrophage phenotype and function may help provide mechanistic insights into disease pathogenesis.

Physical and mechanical regulation of macrophage phenotype and function.

This research examines how a focus on time versus money can lead to two distinct mind‐sets that affect consumers’ willingness to donate to charitable causes. The results of three experiments, conducted both in the lab and in the field, reveal that asking individuals to think about “how much time they would like to donate” (vs. “how much money they would like to donate”) to a charity increases the amount that they ultimately donate to the charity. Fueling this effect are differential mind‐sets activated by time versus money. Implications for the research on time, money, and emotional well‐being are discussed.

/pdf/the-happiness-of-giving-the-time-ask-effect-a463s8rb2d.pdf

Wendy Liu

Papers

Modulation of macrophage phenotype by cell shape

Emergent patterns of growth controlled by multicellular form and mechanics.

Homophily and Latent Attribute Inference: Inferring Latent Attributes of Twitter Users from Neighbors

Physical and mechanical regulation of macrophage phenotype and function.

The Happiness of Giving: The Time-Ask Effect